The role of specific maternal nutritional factors on epigenetic programming of fetal immune development

Manori Amarasekera

    Research output: ThesisDoctoral Thesis

    484 Downloads (Pure)

    Abstract

    [Truncated] The burden of non-communicable diseases (NCD) including cardiovascular, metabolic, allergic and chronic lung diseases has reached pandemic proportions, as the major global health challenge in the 21st century. Understanding the causes and mechanisms of these diverse but pathogenically related inflammatory conditions remains a key challenge in overcoming these trends. The rise in these NCD is strongly related to modern lifestyle changes, and shared environmental risk factors, many of which disrupt early metabolic immune programming and predisposed to subsequent disease.
    The ‘Developmental Origin of Health and Disease’ (DOHaD) paradigm recognises the crucial importance of the early environment in shaping both structural, developmental and physiological response patterns in ways that may determine future health, biological reserve and disease susceptibility. Among many environmental exposures, the quality of early life nutrition is one of the most important factors influencing all aspects of development during critical formative periods, particularly during gestation. While the role of early metabolic adaptations has been long recognised as a predisposing factor, the impact of the early environment on the developing immune system in the subsequent predisposition to inflammation, has only been recognised more recently. Identifying and optimising early factors that influence the patterns of immune development is central in understanding disease pathogenesis and in implementing better prevention strategies. In particular, variations in maternal nutrition can significantly modify both immune and metabolic programming, to determine the long-term health outcomes of the offspring. Only recently has it been recognised that many of these effects are mediated through epigenetic mechanisms such as DNA methylation and histone acetylation. The strong link between changes in the modern diet and escalating rate of allergic and other NCD underscores the importance of identifying specific in utero nutritional exposures affecting the fetal epigenome leading to an altered immune profile.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2015

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